Nutrition, Podcast, Science

Brendan Egan, PhD | EP#407

 September 11, 2023

By  Bernardo Gonçalves

LISTEN TO THE EPISODE HERE:

Brendan Egan - That Triathlon Show

Brendan Egan, PhD, is Associate Professor at Dublin City University. One of the research topics he has investigated extensively is exogenous ketones and exercise performance, and this is also the topic of today's interview.

In this episode you'll learn about:

  • The physiology of ketone bodies and ingestion of exogenous ketones
  • How and why elevated ketone levels through a ketogenic diet and exogenous ketone ingestion are not the same
  • Dosing protocols, and the important differences between ketone esters and ketone salts
  • How does exogenous ketone intake impact endurance performance?
  • How does exogenous ketone intake impact recovery-related outcomes?
  • Practical recommendations for athletes based on current evidence

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Shownotes

Brendan's background

02:11 -

  • I'm currently an associate professor at Dublin City University in Ireland. My academic focus primarily revolves around nutritional metabolism, with a keen interest in performance and exercise physiology. 
  • Over the years, my research has spanned what could be described as molecular exercise science, and I've also delved into exercise and nutrition interventions for older adults.
  • My journey into academia began when I pursued an undergraduate degree in sports and exercise science and a master's in sports nutrition before completing my PhD. 
  • However, I also wear another hat as a performance nutritionist. I've worked in this field for nearly two decades, primarily with athletes in team sports. 
  • While I've dabbled in supporting endurance athletes, I had the opportunity to work with the Irish para-triathlon team for a few years. 
  • I'm most involved with the Irish national football team.
  • My third role is as an athlete with a background in Gaelic football, Ireland's national sport. 
  • I played this relatively less-known game at the highest level I could. 
  • Much of what I discuss in the context of nutrition and performance has been influenced by my experiences and challenges as an athlete.
  • This multifaceted background provides me with a well-rounded perspective, combining academic expertise and practical knowledge gained through personal experiences in sports and nutrition.

Ketones

05:17 -

  • The interest in ketones has been primarily driven by endurance sports, possibly because most of the research up to this point has focused on these sports. 
  • Sponsorship and promotion have also targeted endurance athletes who engage with podcasts and blogs. The initial hype around ketones in 2017-2019 was particularly prominent in professional cycling, which may have influenced the current trend.
  • In the past couple of years, there has been a significant increase in research papers on ketones, with a growing body of knowledge in the field. 
  • A recent review summarizes the ketone research, but new and exciting work continues to emerge.
  • Ketone bodies, including acetoacetate, beta-hydroxybutyrate (BHB), and acetone, are the key focus of discussions on this topic. 
  • These compounds are produced through ketogenesis, driven by a low-carbohydrate, high-fat diet, often called ketogenic. 
  • Ketogenesis primarily occurs in the liver, and specific dietary strategies can increase the production of ketone bodies.
  • Among these ketone bodies, BHB is the one that significantly increases in circulation and is often the main focus of ketone-related discussions. 
  • Ketone supplements aim to increase the concentration of BHB in the bloodstream, and there are various types of supplements designed for this purpose, each with varying degrees of effectiveness.

How ketones are produced

08:19 -

  • Ketogenesis is most pronounced in situations with limited glucose availability, such as during ketogenic diets or fasting periods, typically lasting overnight or up to 18 hours. 
  • In rodents, ketone bodies increase relatively quickly after a few hours of fasting, while in humans, it takes longer. 
  • Classic experiments on ketone metabolism were often conducted during prolonged fasting or starvation scenarios, providing valuable insights into their metabolism.
  • Notably, ketones can be raised directly in the blood by ingesting ketone bodies. However, this approach is not always practical due to factors like taste and the need for pairing with salt. 
  • Another method involves ketone esters, where a ketone body, usually beta-hydroxybutyrate, is bound to a molecule called butane diol. This is significant because butane diol can stimulate ketogenesis. 
  • Other compounds like medium-chain triglycerides and certain amino acids can also enhance ketogenesis in the liver.
  • In summary, beta-hydroxybutyrate (BHB) is the primary focus when discussing the impact of ketone supplements on blood ketone levels. Ketogenesis can be heightened through dietary adjustments and by providing specific dietary supplements.

Ketone salt

10:49 -

  • Ketone bodies exist in their free form within the body, but these free forms can't be ingested directly because they are too acidic and unpalatable. 
  • Manufacturers developed a method to make them more consumable years ago involving binding these acidic ketone molecules with alkaline salts. 
  • They combine ketone bodies like beta-hydroxybutyrate with calcium, magnesium, or potassium salts. 
  • The resulting product is what we commonly know as ketone salts, which are available on the market and typically consist of a mix of beta-hydroxybutyrate and various salts.
  • The challenge with ketone salts is that when you consume them, you also consume a significant amount of salt alongside the ketone body. This can limit their effectiveness in increasing blood beta-hydroxybutyrate (BHB) concentrations because the gastrointestinal system struggles to handle a high salt ion load. 
  • Therefore, ketone salts often do not achieve very high BHB concentration levels compared to other ketone supplements, like ketone esters, unless you have a pure form of ketone salt. I can provide further information if you want more details on purity or other aspects.

Ketone supplements

12:43 -

  • Ketone salts are generally cheaper compared to other ketone products.
  • Ketone concentration in the blood is typically around 0.1 to 0.2 mmol but can increase to 0.3 to 0.5 mmol after extended fasting or a strict ketogenic diet.
  • There's a belief that elevating ketone concentrations above one mmol is necessary for a metabolic effect or potential performance enhancement.
  • A review proposed that a threshold of around one mmol, not exceeding three mmol, might be optimal for ketone effects during exercise.
  • Ketone salts typically raise BHB concentrations to 0.5 and 1 millimolar, which may not reach the desired levels unless taken in very high doses, potentially causing gastrointestinal upset.
  • Some newer, purer ketone salts can achieve slightly higher concentrations but are more expensive.
  • Ketone esters are seen as more potent but are also more expensive (around $30 for a single dose), making them less accessible to the general consumer and more commonly used by professional teams.

Ketone effects

16:45 -

  • Ketone metabolism has been extensively studied and is known to have dramatic effects on various aspects of metabolism, including its use as a potential therapeutic tool in areas like heart failure and anti-catabolic and anti-inflammatory effects.
  • The mechanisms of the ketone body as signalling molecules and their metabolic pathways are relatively well-established in general physiology.
  • However, regarding their effects on sports performance, there is some controversy and knowledge gaps, particularly in understanding how ketone bodies function in skeletal muscle during exercise.
  • One proposed mechanism for the ergogenic potential of ketone bodies is that they can serve as an alternative or additional substrate for energy production in muscles alongside traditional fuels like glucose and free fatty acids.
  • Some studies have suggested that ketone bodies when taken as oral supplements, could contribute a significant percentage (up to 16-18%) of energy provision, although more recent research has revised this estimate to around 5-10%.
  • Another consideration is that ketone bodies may provide a more efficient way to generate ATP (adenosine triphosphate), a crucial energy molecule compared to glucose.
  • These mechanisms and the potential implications for sports performance are subjects of ongoing research and discussion.
  • The evidence regarding the effects of ketone bodies, particularly ketone esters, on human physiology during exercise is somewhat weak and often contradictory. Three main mechanisms have been proposed to explain their impact:
  • Alternative Substrate: Some suggest that ketone bodies might serve as an alternative energy source during exercise. However, the research in this area is inconclusive and doesn't provide explicit support for this hypothesis.
  • Improved Efficiency: Another theory is that ketone bodies could enhance metabolic efficiency during exercise. The body might use them more efficiently than other substrates like carbohydrates. Once again, the evidence is mixed, and there's no definitive conclusion.
  • Reduced Reliance on Carbohydrates: Consuming ketone esters could reduce the body's reliance on carbohydrates as a fuel source during exercise. However, studies have yielded conflicting results on whether ketone esters lead to decreased muscle glycogen utilization.

Differences between exogenous ketones and a ketogenic diet

24:05 - 

  • Ketogenic diets typically result in high concentrations of free fatty acids in the bloodstream and rely heavily on fat oxidation as a fuel source. Conversely, when you consume exogenous ketone supplements, they suppress lipolysis, reducing free fatty acid concentrations. Regarding substrate utilization, exogenous ketone supplementation appears to have a more balanced impact without significant changes in reliance on different fuels.
  • Ketogenic diets have been known to reduce or impair exercise efficiency. However, recent research conducted by the Oxford group demonstrated that when comparing carbohydrates to ketones, cyclists experienced improved cycling efficiency when ketones were ingested. 
  • During a graded exercise test, these cyclists showed enhanced delta efficiency compared to carbohydrate ingestion.
  • It's essential to distinguish between the effects of a ketogenic diet and exogenous ketone supplementation. While both involve the concept of ketones, their metabolic outcomes and impacts on exercise efficiency are distinct. Therefore, assumptions about one based on findings related to the other may not be accurate.

Delta efficiency

26:03 -

  • Growth efficiency relates to the amount of oxygen consumed relative to the energy produced. Delta efficiency, on the other hand, measures changes in efficiency as athletes transition between different stages, typically during incremental tests.
  • Improved efficiency in this context means less oxygen is needed to produce the same work. This concept aligns with the proposed mechanisms of how ketone bodies might affect performance or energy utilization in athletes.
  • An earlier study showed a trend indicating slightly lower oxygen consumption during one hour in participants who consumed ketones and carbohydrates than those who consumed carbohydrates alone. 
  • A new study investigated running economy in well-trained endurance runners under three conditions: carbohydrate alone, carbohydrate plus ketones, and ketones alone. The research aimed to explore the impact of these conditions on running economy and metabolic responses during exercise.
  • The study found that the running economy improved, meaning less oxygen was consumed per unit of work per kilometre per hour in the ketone-only condition. This effect was not observed in the ketone plus carbohydrate condition compared to carbohydrates alone.
  • The study's motivation stemmed from intellectual curiosity, even though some questioned the practical relevance since most athletes primarily use carbohydrates for fuel.
  • The exercise task in our study involved an incremental protocol with six-minute stages. 
  • Participants started running at 10 kilometres per hour for six minutes, then had a brief break to measure lactate levels and take a drink. 
  • Afterwards, they ran six minutes at 11, 12, 13, and 14 kilometres per hour. 
  • During these stages, very few participants exceeded the two mmol lactate threshold. We used these stages to evaluate the run economy at each speed.
  • The data from our study indicate an improvement in run economy in the ketone condition but not in the other two conditions. 
  • However, it's important to note that our study doesn't suggest that people should run solely on ketones. Instead, it was an intellectual exercise to compare the effects of ketone supplements versus carbohydrates.
  • Many previous studies focused on performance outcomes, but we recognized the need to delve into the primary metabolic effects of ketone supplements on factors like run economy. 
  • This study represents a step back to explore these aspects, and the initial findings are intriguing. 
  • The average percentage improvement in run economy was around 4%, similar to when athletes switch from regular shoes to carbon fibre shoes.

Impaired performance in some studies

32:19 -

  • From the early stages of research, there has been a consideration of whether ketone bodies or exogenous ketosis might hinder carbohydrate utilization. 
  • This raises questions about their impact on short-duration, high-intensity efforts that heavily rely on carbohydrates. Potential mechanisms of impairment include carbohydrate interference and factors like increased acidity due to ketone ingestion and potential gastrointestinal discomfort associated with it.
  • In studies exploring the effects of ketone supplementation on performance, there's a more consistent trend of adverse outcomes in shorter-duration exercises, typically lasting around half an hour or less. 
  • These exercises often involve all-out efforts, repeated sprints, or activities with a high reliance on glycolysis. This consistency in adverse effects aligns with the notion that ketone bodies may lower pH levels, making the body more acidic or potentially impair enzymes involved in glycolysis.
  • Apart from efficiency concerns, this concept discusses how a ketogenic diet might impair performance. The prevailing theory suggests that if ketone supplements impair performance, it likely involves mechanisms related to hindering glycolytic pathways or influencing pH levels.
  • The studies in ketone research have been quite diverse in terms of their design, dosing strategies, athlete types, and objectives. 
  • Unlike other fields like carbohydrate research in the 80s and 90s, which had more consolidated designs, ketone studies have varied. 
  • Some examples include studies simulating soccer games, preloading followed by a 10k run, and even investigations involving hypoxia or co-ingestion with bicarbonate. 
  • The use of different supplements, such as ketone salts, medium-chain triglycerides, and butane diol, further complicates the picture.
  • However, it's challenging to identify clear patterns or make definitive conclusions from these studies. 
  • While there's evidence that ketones might impair performance in short-duration events, the effects in longer-duration activities remain uncertain due to the diversity of study designs. 
  • Additionally, ketone esters have become more widely used in research in recent years than other supplements.
  • The lack of standardized study designs and the evolving nature of ketone supplementation make it difficult to draw broad conclusions about its practical implications for athletes and performance. 

Ketone loading protocol

37:27 -

  •  The dosing of ketone esters can vary depending on the specific goals and exercise duration.
  • In many studies, ketone esters are used to enhance performance or endurance during exercise.
  • The original dosing strategy, as seen in a 2016 study from Oxford, involved a larger initial dose just before exercise and a top-up dose during exercise.
  • For exercise lasting longer than an hour, multiple dosing strategies are shared. These typically include an initial dose and smaller top-up doses during the exercise session.
  • Ketone esters elevate ketone concentrations quickly, typically within 15 to 20 minutes after ingestion.
  • The initial dose of ketone esters is often around 20 to 25 grams, based on body mass, taken roughly 20 minutes before exercise.
  • Additional top-up doses, usually similar, may be taken approximately every hour during prolonged exercise.
  • Some debate exists about the dosing strategy for ketone esters, considering whether to provide smaller, more continuous doses throughout exercise, as opposed to the typical pattern of larger doses followed by a decline in ketone levels.
  • Ketone esters are used not only for performance enhancement during exercise but also for recovery and sleep improvement in some cases.

Ketones to improve recovery and sleep

40:52 -

  • In 2017, a review suggested that ketone supplements might potentially aid recovery after exercise due to their impact on glycogen resynthesis and muscle protein synthesis.
  • Despite this suggestion, there have been relatively few studies on ketones' effects on recovery, with only a few examining this aspect.
  • A study from Peter's group looked at ingesting exogenous ketone supplements, specifically ketone esters, during three weeks of intensive training. The study showed that the symptoms of overreaching were reduced, and there were indications of performance benefits in some training sessions.
  • The study involving recreational athletes undergoing intense training was seen as potentially relevant to athletes in endurance events, like grand tours in cycling.
  • Due to their resources and perceived advantages, professional sports teams and athletes may be willing to explore ketone supplements for potential recovery benefits, even if they are costly.
  • Recent research has suggested potential benefits of ketone supplements in terms of sleep quality when taken close to bedtime and in promoting angiogenesis, which is the formation of new blood vessels post-exercise.
  • A growing body of evidence points toward the idea that ketones could be beneficial for recovery, particularly in severe training or sleep quality, or in enhancing the adaptive response to training.
  • Ketone bodies have significant metabolic effects on the body, making their role in recovery plausible.
  • In contrast, using ketone supplements for direct performance enhancement remains uncertain and inconsistent in the research.
  • While there's potential for ketone supplements to impact recovery positively, their direct benefits for performance are less clear at the moment.

Training intensity of the studies

45:16 -

  • During the three-week study, participants underwent various training sessions, including long steady rides, high-intensity interval sessions, and likely a third type of session. 
  • The training regimen was intensive, with most days involving two training sessions. 
  • This resulted in a substantial overall volume of training over the three weeks.
  • Regarding outcome measures, the study focused on several factors. These included heart rate, resting heart rate, and markers in the blood.
  • Performance outcomes were also evaluated through time trials at different stages of the training intervention and an assessment of the training volume completed in the final week.
  • An interesting finding was that despite ketone bodies being thought to be appetite-suppressing, the group using ketone supplements increased their carbohydrate intake by about 15% by the end of the three weeks. 
  • This phenomenon was not observed in the first week, and I'm unsure if it occurred in the second, but it became prominent in the third week.
  • While some critics argue that the increased carbohydrate intake was the primary factor, it's worth considering that the ketone group did experience a notable effect on their appetite. 
  • From a practical standpoint, this increased appetite could benefit individuals subjected to this rigorous training.

Carbohydrate intake

48:43 -

  • Glycogen synthesis can be achieved through carbohydrates alone, provided enough carbohydrates are consumed.
  • When consuming sufficient carbohydrates is difficult, supplementing with protein can be beneficial.
  • In many sports, especially those involving damaging exercise or resistance training, a combination of protein and carbohydrates is often recommended for recovery.
  • Some research has explored whether ketones can have a similar effect to carbohydrates and protein in promoting glycogen synthesis.
  • Studies have shown conflicting results regarding ketones' impact on glycogen synthesis.
  • One study from the Oxford group suggested that combining ketones with glucose infusion benefited glycogen synthesis.
  • However, another study, led by Peter's group in Belgium, found no enhancement in glycogen synthesis when ketones were added to a protein and carbohydrate mixture.
  • Interestingly, research has indicated that ketones may have an anabolic effect and increase muscle protein synthesis.
  • Whether ketones can effectively promote glycogen synthesis remains unresolved, but there is interest in their potential for anabolic or anti-catabolic effects during the post-exercise recovery period.

Potential adverse effects of consuming ketones

51:59 -

  • In earlier studies with ketone supplements, such as ketone esters and ketone mono esters, there were notable concerns about gastrointestinal (GI) distress. 
  • Initially, these studies reported significant adverse effects on GI distress, and researchers were puzzled by this. Subsequent investigations have yielded more varied results.
  • Recent studies have indicated that there may still be slightly worse GI symptoms than using carbohydrates alone when consuming ketone supplements. However, these symptoms are generally not as severe as initially thought. 
  • Changes in the production of ketone esters or the dosage administered in these studies may have influenced the outcomes.
  • In the researcher's own experience, as mentioned at the start of the conversation, they have personally used ketone esters and did not experience any GI upset. 
  • This highlights the individual variability in how people may respond to ketone supplements. Some individuals might experience negative GI responses, while others may not be affected at all.
  • Ultimately, using ketone supplements may be personal, and individuals should try them cautiously. If someone consistently experiences negative GI responses, it may not suit them. 
  • However, it's worth noting that recent research has shown less severe GI distress than earlier studies, suggesting that the technology or understanding of these supplements may have evolved.

Future research

54:44 -

  • We are currently researching the effects of ketone supplementation during exercise. One of our recent observations was an improvement in running economy, especially at lower running speeds, but this improvement was more noticeable when carbohydrates were not being consumed. 
  • This raises the question of the relevance of this effect in different types of exercise challenges.
  • This effect might be particularly relevant for ultra-endurance events and longer distances where carbohydrate availability becomes a limiting factor. 
  • We are conducting a study where participants will run for three hours while consuming carbohydrates or exogenous ketones alone. 
  • In this study, we will evaluate whether the observed improvement in running economy reoccurs and examine factors like fuel utilization, gastrointestinal issues, heart rate, and perceived exertion.
  • It's worth noting that this study is not primarily focused on performance but instead aims to describe the effects during a three-hour run. 
  • However, if we detect promising results, such as improved running economy, we may extend our research to include ultra-distance performance tests.
  • Interestingly, a group in Belgium recently published a paper on using ketone esters during an ultra-endurance race, which provided valuable insights into cognitive function and metabolic responses during longer-duration events. 
  • This suggests that the effects of ketone supplementation may be more pronounced in extended exercise durations.
  • Looking ahead, we find the recovery aspect of ketone supplementation particularly intriguing. We hope to replicate some of the positive effects observed in terms of sleep and recovery, possibly leading to the optimization of protocols. 
  • Based on our current data, ketone supplementation seems unlikely to substantially impact performance during shorter exercise durations.

Research vs Practice

58:12 -

  • I often contemplate the growing interest in ketone supplements, especially when I hear positive anecdotes from individuals connected to the companies producing these supplements. While it's important to consider that the companies themselves may influence these reports and, therefore, somewhat biased, there does appear to be a significant level of enthusiasm surrounding ketone supplements. 
  • Moreover, some professional cycling teams openly acknowledge partnerships with these companies, which further piques my curiosity.
  • One potential explanation for the gap between positive real-world experiences and limited laboratory findings is that most research doesn't focus on elite athletes or those with the highest levels of metabolic fitness. 
  • Exceptionally fit individuals with well-developed mitochondrial function and a predominance of type one muscle fibres might be better suited to utilize ketones effectively. 
  • This leaves me wondering if the disconnect between lab results and practical experiences could be due to insufficient study of elite athletes.
  • On the other hand, it's entirely plausible that elite athletes are using ketone supplements not for performance enhancement but rather for recovery. 
  • The simple explanation could be that these supplements aid post-exercise recovery, a crucial aspect of high-level athletic performance.
  • In essence, the relationship between ketone supplements and athletic performance remains an open-ended question, and the disparity between research and real-world experiences in elite athletes is a complex issue that requires further investigation.
  • In sports nutrition, it's crucial to consider that performance isn't solely about achieving the best time; it also involves managing discomfort and unforeseen issues.
  • For instance, gastrointestinal problems can occur for various reasons, even with carbohydrate-based nutrition. Some athletes might explore alternative fuel sources like the ketogenic diet or ketone supplements, not necessarily to break records but to ensure a more comfortable race experience. 
  • These approaches may allow them to mitigate issues such as upset stomachs or other digestive concerns.
  • Acknowledging that sports nutrition isn't solely geared toward elite athletes is essential. Different individuals have different needs and objectives when it comes to their athletic pursuits. 
  • Therefore, considering a range of strategies, from performance optimization to overall comfort, is a practical and inclusive approach in triathlon and endurance sports.

Ketones with high-level athletes

1:02:02 -

  • In most of our studies, we examine the data to see if individuals who respond positively to a particular intervention are typically the most physically fit. However, we usually do not include this information in our published papers due to the limited sample sizes we work with. 
  • Interestingly, our findings with ketones differ from the patterns seen with nitrate.
  • With nitrate, the benefits appear more pronounced in less fit individuals. 
  • In contrast, the theoretical expectation with ketones is that the benefits would be observed in the most physically fit individuals. 
  • This suggests a different direction of the relationship between the intervention and fitness level. While this is still theoretical, it opens up the possibility that there might be something distinctive about the impact of ketones on highly fit individuals that merits further investigation.

Takeaways from this conversation

1:03:55 -

  • The type of ketone supplement matters, with the working hypothesis being that ketone concentrations should exceed one millimolar.
  • A ketone ester is likely necessary for sustained periods during exercise or post-exercise, but it can be expensive.
  • The likelihood of significant performance benefits from ketones appears slim compared to other supplements like carbohydrates, caffeine, or nitrate.
  • If someone wishes to trial ketone supplements, they can conduct a time trial under similar training and nutrition conditions for comparison.
  • Ketones are unlikely to provide a substantial benefit in short-duration activities.
  • Assessing recovery benefits from ketones is challenging, as it involves subjective measures like perceived sleep quality and recovery.
  • It's difficult to isolate the effects of ketones from other factors when evaluating them over an extended period due to changing fitness levels and lifestyle factors.
  • Conducting experiments on the effectiveness of ketone supplements can be costly, which may be a consideration for individuals with limited budgets.

Rapid-Fire Questions

1:08:02 -
What's your favourite book or resource related to endurance sports?I Podcasts are valuable for gaining advanced knowledge in endurance sports and sports science. (Fast Talk Labs)

What's an important habit you've benefited from athletically, professionally or personally?
Avoiding social media. This has given them more free time and improved focus.

Who's somebody that you look up to or that has inspired you?
My father is as an inspiration despite his involvement in a completely different field (plastics manufacturing). He succeeded in challenging economic times, and despite being over 70 years old, recently won national championships in the 100-meter sprint, long jump, and high jump.

LINKS AND RESOURCES:


Bernardo Gonçalves

Bernardo is a Portuguese elite cyclist and co-founder of SpeedEdge Performance, a company focused on optimising cycling and triathlon performance. He writes the shownotes for That Triathlon Show, and also produces social media content for each new episode.

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